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Introduction The epidemic of prescription opioid overdose and mortality parallels the dispensing rates of prescription opioids, and the availability of increasingly potent opioid analgesics. Objective The common assumption that more potent opioid analgesics are associated with higher rates of adverse outcomes has not been adequately substantiated. We compared the rate of serious adverse events among commonly prescribed opioid analgesics of varying potency. Methods Serious adverse events (SAEs; defined as death, major medical effect, or hospitalization) resulting from exposure to tablets containing seven opioid analgesics (oxycodone, hydrocodone, morphine, hydromorphone, oxymorphone, tapentadol, and tramadol) captured by the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS ® ) System Poison Center Program were evaluated from 2010 through 2016. Rates of SAEs were adjusted for availability through outpatient dispensing data and regressed on morphine milligram equivalents (MME). Results There were 19,480 cases of SAE during the 7-year study period. Hydrocodone and oxycodone contributed to 77% of SAE cases. Comparing rates of outcome by relative potency, a hierarchy was observed with hydromorphone (8.02 SAEs/100 kg) and tapentadol (0.27 SAE/100 kg) as the highest and lowest rates, reflecting a 30-fold difference among individual opioid products. SAE rate and potency were related linearly—SAEs increased 2.04 per 100 kg drug dispensed for each 1-unit rise in MME ( p  = 0.004). Linear regression of SAE/100 kg drug dispensed and drug potency identified that MME comprised 96% of the variation observed. In contrast, potency did not explain variation seen using other study denominators (prescriptions dispensed, dosage units dispensed, and the number of individuals filling a prescription). Conclusions and Relevance Potency of a prescription opioid analgesic demonstrates a significant, highly positive linear relationship with exposures resulting in SAEs per 100 kg drug dispensed reported to poison centers. Potency should be carefully considered from both individual provider and public health perspectives.

Previous research suggests that discrimination is still a prevalent problem within organizations even with the current laws and policies in place in the United States to ensure equality of opportunity for minority groups. Therefore, people of color continue to report experiencing inequality and exclusion in the workplace. The broad purpose of the current investigation is to provide guidance to organizations regarding proactive strategies for mollifying the deleterious consequences that people of color often experience as a result of enduring numerous incidences of subtle discrimination in the workplace. Specifically, I proposed that when people of color report having trusting, supportive relationships with individuals outside their department or relatively-immediate work group, they will be fortified to some extent against feelings of ostracism and inclinations to leave the organization that result from regularly experiencing racial discrimination. Participants were recruited through Prolific and Amazon’s Mechanical Turk and had to identify as a person of color, work at least part time, and live in the United States. The sample included 288 participants with a mean age of 32 years old, nearly equal representation of males and females (50% and 48%, respectively), and the majority of participants were born in the United States (78%). Participants represented a variety of ethnicities with no single ethnicity representing more than twenty-six percent of the total sample. It was hypothesized that holding behaviors will mitigate the negative relationship between discrimination and inclusion as well as the positive association between discrimination and turnover intentions. Results indicated that holding behaviors did not moderate the relationship between discrimination and inclusion (Bmicroaggressions*holding behaviors = .11, p = .46; Bambient discrimination*holding behaviors = .01, p = .72) nor the relationship between discrimination and turnover intentions (Bmicroaggressions*holding behaviors = .27, p = .26; Bambient discrimination*holding behaviors = .01, p = .80). The results of this study provide organizations with practical, effective strategies for fostering inclusive work environments, in which people of color feel like they can express their unique and authentic selves.

More than 250 million children will not meet their developmental potential due to poverty and malnutrition. Psychosocial stimulation has shown promising effects for improving development in children exposed to severe acute malnutrition (SAM) but programs are rarely implemented. In this study, we used qualitative methods to inform the development of a psychosocial stimulation programme to be integrated with SAM treatment in Mwanza, Tanzania. We conducted in-depth interviews with seven caregivers of children recently treated for SAM and nine professionals in early child development. We used thematic content analysis and group feedback sessions and organised our results within the Nurturing Care Framework. Common barriers to stimulate child development included financial and food insecurity, competing time demands, low awareness about importance of responsive caregiving and stimulating environment, poor father involvement, and gender inequality. Caregivers and professionals suggested that community-based support after SAM treatment and counselling on psychosocial stimulation would be helpful, e.g., how to create homemade toys and stimulate through involvement in everyday chores. Based on the findings of this study we developed a context-relevant psychosocial stimulation programme. Some issues identified were structural highlighting the need for programmes to be linked with broader supportive initiatives.

Background Maternal obesity and advanced age have been associated with an increased risk of structural congenital heart defects in the offspring. Whether these factors may also cause abnormalities in infant cardiac dimension and function is unknown. This study investigates whether maternal body mass index (BMI) and maternal age are associated with changes in left ventricular (LV) dimensions and function in the newborn. Methods Infants enrolled in the Copenhagen Baby Heart Study (CBHS), who were born at term, and contributed with a transthoracic echocardiography (TTE) within 60 days of birth were included. The exposure variables were prepregnancy maternal BMI (kg/m 2 ) < 18.5; 18.5–24.9 (reference); 25–29.9; 30–34.9 and ≥ 35 and maternal age (years) < 25; 25–29; 30–34 (reference); 35–39 and ≥ 40. Outcomes were LV parameters ascertained by 2D-echocardiography. Associations between each maternal factor and infant LV parameters were analysed with either a linear model adjusted for the child’s weight and length at birth, gestational age, sex, age at TTE, and maternal smoking, or a linear mixed model, further adjusted for random effects of analyst and month of analysis. Analyses investigating impact of maternal BMI were adjusted for maternal age, and vice versa. Results The study cohort included 24,294 infants. Compared with infants in the BMI reference group, infants born to women with a BMI ≥ 25 kg/m 2 generally had smaller measures of LV internal diameters in end-diastole, reaching statistical significance for BMI 30–34.9 kg/m 2 [-0.11 ± 0.04 mm, p  = 0.01]. All groups of infants born to women with a BMI ≥ 25 kg/m 2 had significantly smaller LV internal diameters in end-systole: BMI 25–29.9 kg/m 2 [-0.04 ± 0.02 mm, p  = 0.04], BMI 30–34.9 kg/m 2 [-0.12 ± 0.03 mm, p  = 0.001] and BMI ≥ 35 kg/m 2 [-0.11 ± 0.05 mm, p  = 0.03]. Compared with infants in the age reference group, infants born to women ≥ 40 years had significantly smaller LV internal diameters in end-diastole [-0.15 ± 0.04 mm, p  = 0.001] and end-systole [-0.09 ± 0.04 mm, p  = 0.009]. Conclusions Systematic population-based echocardiography of infants showed that a maternal prepregnancy BMI ≥ 25 kg/m 2 and maternal age ≥ 40 years were associated with smaller systolic and diastolic LV diameters. The long-term effects are unknown. Clinical trial registration April 2016, Copenhagen Baby Heart, NCT02753348 .

Degeneration of dopamine (DA) neurons in the midbrain underlies the pathogenesis of Parkinson’s disease (PD). Supplement of DA via L-DOPA alleviates motor symptoms but does not prevent the progressive loss of DA neurons. A large body of experimental studies, including those in nonhuman primates, demonstrates that transplantation of fetal mesencephalic tissues improves motor symptoms in animals, which culminated in open-label and double-blinded clinical trials of fetal tissue transplantation for PD 1 . Unfortunately, the outcomes are mixed, primarily due to the undefined and unstandardized donor tissues 1 , 2 . Generation of induced pluripotent stem cells enables standardized and autologous transplantation therapy for PD. However, its efficacy, especially in primates, remains unclear. Here we show that over a 2-year period without immunosuppression, PD monkeys receiving autologous, but not allogenic, transplantation exhibited recovery from motor and depressive signs. These behavioral improvements were accompanied by robust grafts with extensive DA neuron axon growth as well as strong DA activity in positron emission tomography (PET). Mathematical modeling reveals correlations between the number of surviving DA neurons with PET signal intensity and behavior recovery regardless autologous or allogeneic transplant, suggesting a predictive power of PET and motor behaviors for surviving DA neuron number. Rescue of motor and behavioral deficits in a primate model of Parkinson’s disease following autologous transplantation of iPSC-derived dopaminergic neural progenitors without immunosuppression.

The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll‐like receptors to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific and sustained killing of pathogens via B cells, T cells, and antibodies. Traditionally, it has been assumed that innate immunity activates adaptive immunity; however, recent studies have revealed more complex interactions. This review provides a detailed dissection of the composition and function of the innate and adaptive immune systems, emphasizing their synergistic roles in physiological and pathological contexts, providing new insights into the link between these two forms of immunity. Precise regulation of both immune systems at the same time is more beneficial in the fight against immune‐related diseases, for example, the cGAS–STING pathway has been found to play an important role in infections and cancers. In addition, this paper summarizes the challenges and future directions in the field of immunity, including the latest single‐cell sequencing technologies, CAR‐T cell therapy, and immune checkpoint inhibitors. By summarizing these developments, this review aims to enhance our understanding of the complexity interactions between innate and adaptive immunity and provides new perspectives in understanding the immune system. This review begins with a complete description of the composition and function of innate and acquired immunity. On this basis we summarize how the two systems interact and influence disease progression. The paper concludes with a review of therapeutic options and future directions for immune system research.

There are striking sex differences in the prevalence and symptomology of Major Depressive Disorder. Here, we conduct the largest sex-stratified genome wide association and genotype-by-sex interaction meta-analyses of Major Depressive Disorder to date (Females: 130,471 cases, 159,521 controls. Males: 64,805 cases, 132,185 controls). We identify 16 and eight independent genome-wide significant variants in females and males, respectively, including one novel variant on the X chromosome. Major Depressive Disorder in females and males shows substantial genetic overlap with a large proportion of variants displaying similar effect sizes across sexes. However, we also provide evidence for a higher burden of genetic risk in females which could be due to female-specific variants. Additionally, sex-specific pleiotropic effects may contribute to the higher prevalence of metabolic symptoms in females with Major Depressive Disorder. These findings underscore the importance of considering sex-specific genetic architectures in the study of health conditions, including Major Depressive Disorder, paving the way for more targeted treatment strategies. Sex differences are well established in the prevalence and symptoms of depression. Here, the authors identify a novel X chromosome variant, greater genetic risk, and stronger links to metabolic traits in females, highlighting the importance of sex-aware approaches.

B cells secrete antibodies and mediate the humoral immune response, making them extremely important in protective immunity against SARS-CoV-2, which caused the coronavirus disease 2019 (COVID-19) pandemic. In this review, we summarize the positive function and pathological response of B cells in SARS-CoV-2 infection and re-infection. Then, we structure the immunity responses that B cells mediated in peripheral tissues. Furthermore, we discuss the role of B cells during vaccination including the effectiveness of antibodies and memory B cells, viral evolution mechanisms, and future vaccine development. This review might help medical workers and researchers to have a better understanding of the interaction between B cells and SARS-CoV-2 and broaden their vision for future investigations.

We describe hepatitis C testing of 47 (2%) of 2,266 children diagnosed with perinatal hepatitis C who were exposed during 2018-2020 in 7 jurisdictions in the United States. Expected frequency of perinatal transmission is 5.8%, indicating only one third of the cases in this cohort were reported to public health authorities.

Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses 1 , 2 and can function as bona fide antigens that facilitate tumour rejection 3 . Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma 4 – 6 , is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load 1 , 7 and an immunologically ‘cold’ tumour microenvironment 8 . We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study. Patients who did not receive dexamethasone—a highly potent corticosteroid that is frequently prescribed to treat cerebral oedema in patients with glioblastoma—generated circulating polyfunctional neoantigen-specific CD4 + and CD8 + T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumour-infiltrating T cells. Using single-cell T cell receptor analysis, we provide evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma. Neoantigen-targeting vaccines are a feasible therapy for tumours with a low mutation burden and immunologically ‘cold’ tumour microenvironment, as neoantigen-specific T cells from the peripheral blood migrate into intracranial glioblastoma, thereby altering the immune milieu of the glioblastoma.